While studying at Italia Conti, Gillan was scouted by a modelling agency[5] and modelled in the launch party of Nicola Roberts' Dainty Doll Make-Up Range.[citation needed] Gillan has said she would not give up her acting career to return to modelling, stating that she enjoyed modelling but acting was always her main interest and goal.[6]

Gillan's early television acting career included guest appearances on several drama series, with her first role being in an episode of Rebus, a role she obtained while still at Italia Conti.[7] Gillan then undertook a two-year stint as a member of the ensemble cast of the sketch comedy series The Kevin Bishop Show, in which she played multiple characters including celebrities such as Katy Perry and Angelina Jolie. She appeared in the Channel 4 film Stacked, playing the role of Ginny.[8] Gillan also appeared on TV in a leading role in a horror project entitled The Well, which was broadcast as a series of episodic short films on BBC Two and later as a web series on BBC.co.uk. Part of the BBC's multimedia "switch" programming, the short episodes interconnect with online games that further explore the environments presented in the series.[9]

Gillan starred in the lead role in the supernatural horror movie Oculus, which was filmed in Alabama and released in April 2014.[24] She also revealed that she has been cast in comedian Charlie Brooker's TV series A Touch of Cloth.[25] Gillan has also been cast in a film titled The List which began filming in Los Angeles in May 2013.

Gillan joined the regular cast of Adult Swim's NTSF:SD:SUV:: for the show's third season in 2013.[29][30] In November 2013 Gillan appeared on Broadway in a play called Time to Act, one of the plays included in "The 24 Hour Plays on Broadway" to benefit the non-profit Urban Arts Partnership.[31]

In February 2014, Gillan was cast as the lead in Selfie, an American single-camera sitcom for ABC, which is produced by Warner Bros. Television and was greenlit for the 2014–15 US television season. Gillan played a social media-obsessed socialite named Eliza Dooley, a modern-day take on the main character from My Fair Lady, Eliza Doolittle. This is Gillan's first time starring in the lead role of an American television series.[32][33][34] The series was cancelled by ABC on 7 November 2014 after seven episodes;[35] the remaining six episodes were made available on Hulu starting 25 November 2014.[36]

Gillan wrote and directed her first short film, Coward, which went on to win Best Independent Short at the Independent Film-makers Showcase at the Beverly Hills Film Festival 2015.[40] The film also screened at the 2015 Edinburgh Film Festival.[41]

Gillan made her debut in writing, directing, and producing with her short film, Coward, which premiered at Edinburgh International Film Festival, and nominated for several awards. Later in the year she wrote, directed, and starred in another short film called Conventional.[45] On November 2, 2016, it was announced that Gillan will direct and star in her feature directorial debut with Burbank-based development and production company Mt. Hollywood Films' indiedrama project titled Tupperware Party. The film is scheduled to start shooting in January 2017 in Scotland.[46]

She has stated that, though her family is Catholic, she was never baptized and is not religious, instead agreeing with the statement that, "we're just minuscule dots in the vast cosmic emptiness of the universe".[50]